pharmacodynamics I Flashcards

1
Q

pharmacodynamics is the study of _____

A

biochemical & physiological effects of drugs at the receptor level
&
the response produced due to drug-receptor interactions

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2
Q

the 3D arrangement of receptors is the result of _____

A

their primary, secondary, tertiary, & quaternary structures

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3
Q

5 binding forces involved in drug-receptor interactions (listed in order from strongest to weakest), which one is irreversible

A

-covalent bond (irreversible)
-ionic bond
-hydrogen bond
-hydrophobic interactions
-van der waals bond

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4
Q

what is a covalent bond

A

2 atoms share a pair of electrons

long-lasting, irreversible

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5
Q

what is an ionic bond

A

electrostatic attraction forces between charged ions

reversible

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6
Q

what is a hydrogen bond

A

a proton accepts an e- from a donor like O or N

reversible

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7
Q

what is a van der waals bond

A

attractive forces between nonpolar molecules

very weak

reversible

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8
Q

what are hydrophobic interactions

A

tendency of nonpolar molecules to interact w each other

important for lipid soluble drugs

reversible

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9
Q

what is an agonist

A

an agent that binds a receptor & produces a signal

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10
Q

what is an antagonist

A

an agent that binds a receptor & prevents the agonist from producing an effect

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11
Q

receptors mediate the actions of _____

A

agonists & antagonists

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12
Q

orthosteric site vs allosteric site

A

orthosteric site- where a drug binds if it’s the same site as the endogenous agonist

allosteric site- where a drug binds on a different region of the receptor

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13
Q

what is a primary agonist

A

drug that binds to the orthosteric site

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14
Q

what is an allosteric modulator

A

drug that binds to the allosteric site

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15
Q

4 receptor superfamilies

A

-ionotropic receptors
-metabotropic receptors
-enzyme-linked receptors
-intracellular receptors

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16
Q

ionotropic receptors

-structure
-binding site
-how they’re opened

A

receptors coupled to ion channels

-4-5 subunits surrounding central core
-binding site: large extracellular N-terminal
-opened via:
ligand, voltage, OR 2nd messenger regulated

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17
Q

metabotropic receptors

-structure
-binding site

A

indirectly coupled to G-proteins

-single polypeptide chain; 7 transmembrane alpha helices & 4 intracellular domains
-binding site: transmembrane helices

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18
Q

enzyme-linked receptors

-receptors for what
-where are the effects seen
-structure
-binding site

A

-receptors for growth factors, cytokines, insulin
-effects are exerted at gene transcription level
-only 1 helical transmembrane subunit
-binding site: extracellular N-terminus

19
Q

intracellular receptors, type I

-what binds to them
-located where

A

have targets for sex hormones & glucocortioid

-located in cytoplasm, bound to hsp90

20
Q

intracellular receptors, type II

-what binds to them
-located where

A

have targets for thyroid hormone, vitamin A & D, & retinoid

-located in nucleus

21
Q

2 categories of mammalian G-proteins

A

heterotrimeric G-proteins

small G-proteins

22
Q

when a ligand can bind many different _____ to produce specific effects

A

receptor subtypes

23
Q

homologous desensitization mechanism (2 stages)

A

(agonist-dependent desensitization)

1) GRKs 1-7 phosph agonist-occupied GPCRs (1st stage can be reversed)
2) the phosph increases affinity for Arrestins to bind = maximal homologous desensitization (receptor can no longer bind G-protein & is endocytosed)

24
Q

what does GRK stand for

A

G-protein coupled receptor kinase

25
heterologous desensitization mechanism
(agonist-independent desensitization) 1) second messenger-dependent kinases (PKA, PKC) phosph both agonist-stimulated & non-stimulated GPCRs = 40-50% loss of receptor function
26
2 types of rapid desensitization that can occur for GPCRs (G-protein coupled receptors), & how do these occurs
homologous heterologous both occur via protein phosphorylation
27
PKA, PKC during heterologous desensitization phosph _____
sites different from GRKs
28
regulation of receptor function at receptor level
down-regulation up-regulation
29
regulation of receptor function at post-receptor level
homologous / heterologous desensitization
30
what is down-regulation, relating to receptor-level regulation
persistent agonist stimulation by endogenous neurotransmitter / synthetic agonist = decrease in receptor number
31
what is up-regulation, relating to receptor-level regulation
chronic deprivation of receptor excitation by lack of endogenous neurotransmitter / persistent antagonist = increase in receptor number
32
another word for desensitization
tachyphylaxis
33
heterotrimeric G-proteins
alpha, beta, gamma subunits alpha subunit = binds & hydrolyzes beta, gamma subunits = hydrophobic, form a beta-gamma complex
34
small G-proteins
monomeric belong to Ras superfamily of GTPases
35
heterogeneity of G-proteins allows _____
different receptors to exert opposite effects on a target enzyme
36
examples of metabotropic receptors
5-HT2 muscarinic M1 dopamine D2
37
exampls of ionotropic receptors
GABA a 5-HT3
38
6 examples of 2nd messengers for G-proteins
cAMP cGMP IP3 PIP2 DAG Ca2+
39
3 examples of 3rd messengers for G-proteins
PKA PKC PKG
40
5 examples of intracellular targets of G-proteins
adenylyl cyclases (9 types) guanylyl cyclases (2 types) phospholipase C (13 types) phospholipase A (A1, A2) ion channels
41
serotonin receptors
5-HT
42
serotonin receptor whose activation causes anxiety
5-HT1A
43
serotonin receptor whose activation causes hallucinations / depression
5-HT2A
44
serotonin receptor whose activation causes vomiting
5-HT3